Document Report Card

ID: ALA5136961

Journal: RSC Med Chem

Title: Deglycase-activity oriented screening to identify DJ-1 inhibitors.

Authors: Maksimovic I, Finkin-Groner E, Fukase Y, Zheng Q, Sun S, Michino M, Huggins DJ, Myers RW, David Y.

Abstract: The oncoprotein and Parkinson's disease-associated enzyme DJ-1/PARK7 has emerged as a promiscuous deglycase that can remove methylglyoxal-induced glycation adducts from both proteins and nucleotides. However, dissecting its structural and enzymatic functions remains a challenge due to the lack of potent, specific, and pharmacokinetically stable inhibitors targeting its catalytic site (including Cys106). To evaluate potential drug-like leads against DJ-1, we leveraged its deglycase activity in an enzyme-coupled, fluorescence lactate-detection assay based on the recent understanding of its deglycation mechanism. In addition, we developed assays to directly evaluate DJ-1's esterase activity using both colorimetric and fluorescent substrates. The resulting optimized assay was used to evaluate a library of potential reversible and irreversible DJ-1 inhibitors. The deglycase activity-oriented screening strategy described herein establishes a new platform for the discovery of potential anti-cancer drugs.

CiteXplore: 34355187

DOI: 10.1039/D1MD00062D